A selective requirement for copper-dependent activation of cytochrome c oxidase by Cox17p

Koichiro Kako, Akio Takehara, Hidenori Arai, Takashi Onodera, Yoshinori Takahashi, Hiroshi Hanagata, Yasumitsu Ogra, Hiroaki Takagi, Hiroko Kodama, Kazuo T. Suzuki, Eisuke Munekata, Akiyoshi Fukamizu

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Cox17p is cloned from yeast as a chaperone to deliver copper to the mitochondria of assembly for cytochrome c oxidase (CCO). In mammals, CCO is a key enzyme for cellular respiration and a defect in its function is associated with severe neonatal or infantile lactic acidosis and early death. Recently, we found that Cox17p is not only required for mitochondrial oxidative phosphorylation but also is essential for embryonic growth and development in COX17 gene-deficient mice. To investigate its biochemical features, recombinant human Cox17p was overexpressed and purified without a purification tag. It specifically binds Cu(I) at a molar copper content of 3.3 ± 0.04 under reduced conditions and significantly activates the mitochondrial CCO in vitro. Although the Cu-Cox17p complex was maintained between pH values from 5.0 to 7.7, Cu was completely released from Cox17p at pH 8.0. An acute exposure of excess amount of copper ion to mouse cells resulted in a significant reduction of Cox17p mRNA expression, whereas copper starvation maintained the Cox17p transcription level. These results suggest that the stringent selectivity of Cox17p for copper is required for CCO activation, to prevent copper overload, or promote the supply of copper.

Original languageEnglish (US)
Pages (from-to)1379-1385
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume324
Issue number4
DOIs
StatePublished - Nov 26 2004

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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